Relationships between genes controlling the immune response and structural genes which code for antibody H and L chains will be investigated. Rabbits heterozygous for certain light chain allotypes preferentially select one of these group b allotypes in the synthesis of antibodies directed against the streptococcal carbohydrates. Several experimental approaches are being used to determine the basis of this allelic selection. Relative binding affinities of b4 and b9 antibodies for the streptococcal antigens were compared and it was found that b9 antibodies had significantly higher affinities than the b4. Thus it appears that antibodies with the higher affinities are being selected against in this process. Streptococcal antibodies raised in rabbits heterozygous for other group b allotype combinations showed no such selection of allotype b4. Similarly, fractions with differing affinity in the nonselected cases show equal distributions of both allotypes throughout the various fractions. A sensitive radioimmunoassay for rabbit beta-2 microglobulin has been developed and levels of beta-2 microglobulin were measured for various antistreptococcal sera. It was found that levels rose 2 to 5 times normal levels in the immunization period. Current efforts aim at identification of the molecules that are associated with the beta-2 microglobulin and comparison of these molecules in normal and antistreptococcal sera.